Climate Spaces and Cliffs: A Novel Bovine Thermodynamic and Mass Balances Model.

The effects of climate change on animals are typically viewed in terms of survivability and wellbeing. In this study, we broaden that purview to include climate impacts on reproductive capability. There are not only climate spaces for daily function, but climate cliffs that represent reproductive failures in the face of climate warming.

Incorporating species-specific morphology improves model predictions of thermal and hydric stress in the sand fiddler crab, Leptuca pugilator.

Understanding where and why organisms are experiencing thermal and hydric stress is critical for predicting species' responses to climate change. Biophysical models that explicitly link organismal functional traits like morphology, physiology, and behavior to environmental conditions can provide valuable insight into determinants of thermal and hydric stress. Here we use a combination of direct measurements, 3D modeling, and computational fluid dynamics to develop a detailed biophysical model of the sand fiddler crab, Leptuca pugilator.

Behavioural responses of a large, heat-sensitive mammal to climatic variation at multiple spatial scales.

Climate warming creates energetic challenges for endothermic species by increasing metabolic and hydric costs of thermoregulation. Although endotherms can invoke an array of behavioural and physiological strategies for maintaining homeostasis, the relative effectiveness of those strategies in a climate that is becoming both warmer and drier is not well understood. In accordance with the heat dissipation limit theory which suggests that allocation of energy to growth and reproduction by endotherms is constrained by the ability to dissipate heat, we expected that patterns of habitat use by large, heat-sensitive mammals across multiple scales are critical for behavioural thermoregulation during periods of potential heat stress and that they must invest a large portion of time to maintain heat balance.

Physiological costs of undocumented human migration across the southern United States border.

Political, economic, and climatic upheaval can result in mass human migration across extreme terrain in search of more humane living conditions, exposing migrants to environments that challenge human tolerance. An empirical understanding of the biological stresses associated with these migrations will play a key role in the development of social, political, and medical strategies for alleviating adverse effects and risk of death. We model physiological stress associated with undocumented migration across a commonly traversed section of the southern border of the United States and find that locations of migrant death are disproportionately clustered within regions of greatest predicted physiological stress (evaporative water loss).

North Atlantic winter cyclones starve seabirds.

Each winter, the North Atlantic Ocean is the stage for numerous cyclones, the most severe ones leading to seabird mass-mortality events called "winter wrecks." During these, thousands of emaciated seabird carcasses are washed ashore along European and North American coasts. Winter cyclones can therefore shape seabird population dynamics by affecting survival rates as well as the body condition of surviving individuals and thus their future reproduction.

Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.

The beta-site APP cleaving enzyme 1, known as BACE1, has been a widely pursued Alzheimer's disease drug target owing to its critical role in the production of amyloid-beta. We have previously reported the clinical development of LY2811376 and LY2886721. LY2811376 advanced to Phase I before development was terminated due to nonclinical retinal toxicity.

Meeting Paris agreement objectives will temper seabird winter distribution shifts in the North Atlantic Ocean.

We explored the implications of reaching the Paris Agreement Objective of limiting global warming to <2°C for the future winter distribution of the North Atlantic seabird community. We predicted and quantified current and future winter habitats of five North Atlantic Ocean seabird species (Alle alle, Fratercula arctica, Uria aalge, Uria lomvia and Rissa tridactyla) using tracking data for ~1500 individuals through resource selection functions based on mechanistic modeling of seabird energy requirements, and a dynamic bioclimate envelope model of seabird prey. Future winter distributions were predicted to shift with climate change, especially when global warming exceed 2°C under a "no mitigation" scenario, modifying seabird wintering hotspots in the North Atlantic Ocean.

Field data confirm the ability of a biophysical model to predict wild primate body temperature.

In the face of climate change there is an urgent need to understand how animal performance is affected by environmental conditions. Biophysical models that use principles of heat and mass transfer can be used to explore how an animal's morphology, physiology, and behavior interact with its environment in terms of energy, mass and water balances to affect fitness and performance. We used Niche Mapper™ (NM) to build a vervet monkey (Chlorocebus pygerythrus) biophysical model and tested the model's ability to predict core body temperature (T) variation and thermal stress against T and behavioral data collected from wild vervets in South Africa.

Infrared thermography cannot be used to approximate core body temperature in wild primates.

Understanding the physiological processes that underpin primate performance is key if we are to assess how a primate might respond when navigating new and changing environments. Given the connection between a mammal's ability to thermoregulate and the changing demands of its thermal environment, increasing attention is being devoted to the study of thermoregulatory processes as a means to assess primate performance. Infrared thermography can be used to record the body surface temperatures of free-ranging animals.

High accuracy gene expression profiling of sorted cell subpopulations from breast cancer PDX model tissue.

Intratumor Heterogeneity (ITH) is a functionally important property of tumor tissue and may be involved in drug resistance mechanisms. Although descriptions of ITH can be traced back to very early reports about cancer tissue, mechanistic investigations are still limited by the precision of analysis methods and access to relevant tissue sources. PDX models have provided a reproducible source of tissue with at least a partial representation of naturally occurring ITH.

Future winters present a complex energetic landscape of decreased costs and reduced risk for a freeze-tolerant amphibian, the Wood Frog (Lithobates sylvaticus).

Winter climate warming is rapidly leading to changes in snow depth and soil temperatures across mid- and high-latitude ecosystems, with important implications for survival and distribution of species that overwinter beneath the snow. Amphibians are a particularly vulnerable group to winter climate change because of the tight coupling between their body temperature and metabolic rate. Here, we used a mechanistic microclimate model coupled to an animal biophysics model to predict the spatially explicit effects of future climate change on the wintering energetics of a freeze-tolerant amphibian, the Wood Frog (Lithobates sylvaticus), across its distributional range in the eastern United States.

Landscape scale thermoregulatory costs from sublethal exposure to Deep Water Horizon oil in the double-crested cormorant.

Toxic effects of heavy oiling to wildlife are well known from oil spills, although sublethal oil exposure effects are poorly understood. We used Niche Mapper™, to compute spatially and temporally specific energetic and behavioral impacts of repeated sublethal oil exposure to double-crested cormorants (Phalacrocorax auritus). During winter (October-March) cormorants exposed to 13 g, 39 g, and 65-78 g of oil, had on average a 31%, 59%, and 76% predicted increase in total resting energetic requirements (RMR) compared to unoiled birds, respectively.

Modeling Dragons: Using linked mechanistic physiological and microclimate models to explore environmental, physiological, and morphological constraints on the early evolution of dinosaurs.

We employed the widely-tested biophysiological modeling software, Niche Mapper™ to investigate the metabolic function of the Late Triassic dinosaurs Plateosaurus and Coelophysis during global greenhouse conditions. We tested a variety of assumptions about resting metabolic rate, each evaluated within six microclimate models that bound paleoenvironmental conditions at 12° N paleolatitude, as determined by sedimentological and isotopic proxies for climate within the Chinle Formation of the southwestern United States. Sensitivity testing of metabolic variables and simulated "metabolic chamber" analyses support elevated "ratite-like" metabolic rates and intermediate "monotreme-like" core temperature ranges in these species of early saurischian dinosaur.

Evaporative water loss simulation improves models' prediction of habitat suitability for a high-elevation forest skink.

Accurate evaluation of habitat availability for wildlife is relevant for ecological applications. Researchers have frequently used models to simulate habitats thermally suitable for reptiles, but these results have limited application for species highly selective for habitat humidity. Here, we use the biophysical Niche Mapper™ model to investigate impacts of vegetation cover on the habitat quality of a high-elevation forest skink, Sphenomorphus taiwanensis, and to predict changes in habitat suitability in a future warmer climate (3 °C increase in air temperature).

Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints.

Inhibition of BACE1 has become an important strategy in the quest for disease modifying agents to slow the progression of Alzheimer's disease. We previously reported the fragment-based discovery of LY2811376, the first BACE1 inhibitor reported to demonstrate robust reduction of human CSF Aβ in a Phase I clinical trial. We also reported on the discovery of LY2886721, a potent BACE1 inhibitor that reached phase 2 clinical trials.

Climate change could overturn bird migration: Transarctic flights and high-latitude residency in a sea ice free Arctic.

Climate models predict that by 2050 the Arctic Ocean will be sea ice free each summer. Removing this barrier between the Atlantic and the Pacific will modify a wide range of ecological processes, including bird migration. Using published information, we identified 29 arctic-breeding seabird species, which currently migrate in the North Atlantic and could shift to a transarctic migration towards the North Pacific.

Correction: Flow based single cell analysis of the immune landscape distinguishes Barrett's esophagus from adjacent normal tissue.

[This corrects the article DOI: 10.18632/oncotarget.26911.

Evaporative cooling provides a major metabolic energy sink.

Objective: Elimination of food calories as heat could help redress the excess accumulation of metabolic energy exhibited as obesity. Prior studies have focused on the induction of thermogenesis in beige and brown adipose tissues as the application of this principle, particularly because the β-adrenergic environment associated with thermogenic activation has been shown to have positive health implications. The counterpoint to this strategy is the regulation of heat loss; we propose that mammals with inefficient heat conservation will require more thermogenesis to maintain body temperature.

Flow based single cell analysis of the immune landscape distinguishes Barrett's esophagus from adjacent normal tissue.

Barrett's esophagus (BE) is metaplasia of the squamous epithelium to a specialized columnar epithelium. BE progresses through low- and high-grade dysplasia before developing into esophageal adenocarcinoma. The BE microenvironment is not well defined.

Shifts in metabolic fuel use coincide with maximal rates of ventilation and body surface rewarming in an arousing hibernator.

It is well established that hibernating mammals rely predominantly on lipid stores to fuel metabolism throughout the hibernation season. However, it is unclear if other endogenous fuels contribute to the rapid, ~400-fold increase in metabolic rate during the early phase of arousal from torpor. To investigate this issue, we used cavity ring-down spectroscopy, a technique that provides a real-time indication of fuel use by measuring the ratio of C to C in the exhaled CO of arousing 13-lined ground squirrels ().

Modulation of TARP 8-Containing AMPA Receptors as a Novel Therapeutic Approach for Chronic Pain.

Nonselective glutamate -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists are efficacious in chronic pain but have significant tolerability issues, likely arising from the ubiquitous expression of AMPA receptors in the central nervous system (CNS). Recently, LY3130481 has been shown to selectively block AMPA receptors coassembled with the auxiliary protein, transmembrane AMPA receptor regulatory protein (TARP) 8, which is highly expressed in the hippocampus but also in pain pathways, including anterior cingulate (ACC) and somatosensory cortices and the spinal cord, suggesting that selective blockade of 8/AMPA receptors may suppress nociceptive signaling with fewer CNS side effects. The potency of LY3130481 on recombinant 8-containing AMPA receptors was modulated by coexpression with other TARPs; 2 subunits affected activity more than 3 subunits.

Mechanistic modeling of environmental drivers of woolly mammoth carrying capacity declines on St. Paul Island.

On St. Paul Island, a remnant of the Bering Land Bridge, woolly mammoths persisted until 5,600 yr BP with no known predators or competitors, providing a natural system for studying hypothesized environmental drivers of extinction. These include overheating due to rising temperatures, starvation, and drought.

Experimental and modeled thermoregulatory costs of repeated sublethal oil exposure in the Double-crested Cormorant, Phalacrocorax auritus.

To fully understand the impact of oil exposure, it is important to understand sublethal effects like how increased thermoregulatory costs may affect survival and reproduction. However, it is difficult and time-consuming to measure these effects in wild animals. We present a novel use of a bioenergetics model, Niche Mapper™, to estimate thermoregulatory impacts of oiling, using data from captive Double-crested Cormorants (Phalacrocorax auritus) experimentally exposed to oil.

Reflection of near-infrared light confers thermal protection in birds.

Biologists have focused their attention on the optical functions of light reflected at ultraviolet and human-visible wavelengths. However, most radiant energy in sunlight occurs in 'unseen' near-infrared (NIR) wavelengths. The capacity to reflect solar radiation at NIR wavelengths may enable animals to control heat gain and remain within their critical thermal limits.

An ecophysiological perspective on likely giant panda habitat responses to climate change.

Threatened and endangered species are more vulnerable to climate change due to small population and specific geographical distribution. Therefore, identifying and incorporating the biological processes underlying a species' adaptation to its environment are important for determining whether they can persist in situ. Correlative models are widely used to predict species' distribution changes, but generally fail to capture the buffering capacity of organisms.